Hybrid reaction-diffusion and clock-and-wavefront model for the arrest of oscillations in the somitogenesis segmentation clock

TL;DR

This paper introduces a hybrid model combining reaction-diffusion and clock-and-wavefront mechanisms to better explain somitogenesis, addressing limitations of existing models by integrating local interactions with global positional cues.

Contribution

It develops a hybrid model that couples reaction-diffusion dynamics with a morphogen gradient, improving robustness and biological realism over previous models.

Findings

The hybrid model overcomes sensitivity issues of the Meinhardt-PORD model.

It better explains experimental observations incompatible with traditional models.

The model integrates local and global mechanisms for somitogenesis.

Abstract

The clock and wavefront paradigm is arguably the most widely accepted model for explaining the embryonic process of somitogenesis. According to this model, somitogenesis is based upon the interaction between a genetic oscillator, known as segmentation clock, and a differentiation wavefront, which provides the positional information indicating where each pair of somites is formed. Shortly after the clock and wavefront paradigm was introduced, Meinhardt presented a conceptually different mathematical model for morphogenesis in general, and somitogenesis in particular. Recently, Cotterell et al. rediscovered an equivalent model by systematically enumerating and studying small networks performing segmentation. Cotterell et al. called it a progressive oscillatory reaction-diffusion (PORD) model. In the Meinhardt- PORD model, somitogenesis is driven by short-range interactions and the posterior movement of the front is a local, emergent phenomenon, which is not controlled by global positional information. With this model, it is possible to explain some experimental observations that are incompatible with the clock and wavefront model. However the Meinhardt-PORD model has some important disadvantages of its own. Namely, it is quite sensitive to fluctuations and depends on very specific initial conditions (which are not biologically realistic). In this work, we propose an equivalent Meinhardt-PORD model, and then amend it to couple it with a wavefront consisting of a receding morphogen gradient. By doing so, we get a hybrid model between the Meinhardt-PORD and the clock-and-wavefront ones, which overcomes most of the deficiencies of the two originating models.